• Does the JNK/Jun Signaling Node Regulate Autophagy in Breast Cancer Cells?

      Joseph, Carol; Department of Cellular Biology and Anatomy; Schoenlein, Patricia V.; Department of Cellular Biology and Anatomy; Augusta University (2018-02-12)
      A common treatment for estrogen receptor positivebreast cancers is the use of selective estrogen receptor modulators such as Tamoxifen.1Unfortunately, 30-40% of patients experience relapse due tothe development ofantiestrogen resistance. Autophagy, a process that is typically seen in cells that are exposed to a variety of stresses, is critical to development of antiestrogen resistanceand may play a key role in metastatic progression.2,3 To further combat antiestrogen resistance, a potential target for breast cancers is JNK (c-Jun N-terminal kinase), a member of the mitogen-activated protein kinase (MAPK) family. The mechanismsby which JNK inhibition affects breast cancer cell growthare not fully characterized.Our hypothesis is that JNK is a key regulator of autophagy and the emergence of autophagy-dependent antiestrogen resistant breast cancer. Our aims are todetermine the effect of JNK inhibition on autophagy, cell number, and cell viability under conditions of antiestrogen treatment.By utilizingMCF-7breast cancercells andthe irreversible JNK-IN-8 inhibitor our current data provides strong evidence that JNK inhibition blocks autophagy. Data supporting a role for JNK in the regulation of antiestrogen-mediated autophagy have the potential to identify JNK as a molecular target for the improved treatment of breast cancer.